Functions of the Signal Transducer and Activator of Transcription 6 in a Behavioral Animal Model of Depression

Nam, Sun‐Young; Kim, Hee-Yun; Lee, Hyung Eun; Ryu, Jong Hoon; Jang, Jae-Bum; Kim, Hyung-Min; Jeong, Hyun-Ja

doi:10.1159/000487954

Cited by 2 publications

(2 citation statements)

References 15 publications

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“…Eomes is highly expressed in the cerebellum compared to the frontal cortex and is associated with neurodevelopment [ 97 ]. Stat6 was under-expressed in Hi relative to Co mice and this pattern is consistent with reports that Stat6-deficient mice exhibited lower immobility time in the forced swimming test relative to wild type mice [ 98 ].…”

Section: Resultssupporting

confidence: 90%

Brain region-dependent gene networks associated with selective breeding for increased voluntary wheel-running behavior

et al. 2018

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Mouse lines selectively bred for high voluntary wheel-running behavior are helpful models for uncovering gene networks associated with increased motivation for physical activity and other reward-dependent behaviors. The fact that multiple brain regions are hypothesized to contribute to distinct behavior components necessitates the simultaneous study of these regions. The goals of this study were to identify brain-region dependent and independent gene expression patterns, regulators, and networks associated with increased voluntary wheel-running behavior. The cerebellum and striatum from a high voluntary running line and a non-selected control line were compared. Neuropeptide genes annotated to reward-dependent processes including neuropeptide S receptor 1 (Npsr1), neuropeptide Y (Npy), and proprotein convertase subtilisin/kexin type 9 (Pcsk9), and genes implicated in motor coordination including vitamin D receptor (Vdr) and keratin, type I cytoskeletal 25 (Krt25) were among the genes exhibiting activity line-by-region interaction effects. Genes annotated to the Parkinson pathway presented consistent line patterns, albeit at different orders of magnitude between brain regions, suggesting some parallel events in response to selection for high voluntary activity. The comparison of gene networks between brain regions highlighted genes including transcription factor AP-2-delta (Tfap2d), distal-less homeobox 5 gene (Dlx5) and sine oculis homeobox homolog 3 (Six3) that exhibited line differential expression in one brain region and are associated with reward-dependent behaviors. Transcription factors including En2, Stat6 and Eomes predominated among regulators of genes that differed in expression between lines. Results from the simultaneous study of striatum and cerebellum confirm the necessity to study molecular mechanisms associated with voluntary activity and reward-dependent behaviors in consideration of brain region dependencies.

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Section: Resultssupporting

confidence: 90%

Brain region-dependent gene networks associated with selective breeding for increased voluntary wheel-running behavior

et al. 2018

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“…Interestingly, STAT6 exhibited one of the highest scores based on the five functional annotations in the present study. Several previous studies support the role of STAT6 in depression; these were validated in a preclinical investigation, in which STAT6 signaling was discovered to be involved in some of the brain’s mechanisms, such as the activity of neurons and neuroplasticity [ 119 , 120 ]. Previous studies using animal models emphasized that a deficiency of STAT6 decreases levels of dopamine and serotonin transporter; thus, STAT6 is suggested to play a pivotal role in the pathogenesis of depression through monoamine regulation in the hippocampus of the brain [ 119 , 121 ].…”

Section: Discussionmentioning

confidence: 82%

Genomic-Analysis-Oriented Drug Repurposing in the Search for Novel Antidepressants

Lesmana

Chiu

et al. 2022

Biomedicines

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From inadequate prior antidepressants that targeted monoamine neurotransmitter systems emerged the discovery of alternative drugs for depression. For instance, drugs targeted interleukin 6 receptor (IL6R) in inflammatory system. Genomic analysis-based drug repurposing using single nucleotide polymorphism (SNP) inclined a promising method for several diseases. However, none of the diseases was depression. Thus, we aimed to identify drug repurposing candidates for depression treatment by adopting a genomic-analysis-based approach. The 5885 SNPs obtained from the machine learning approach were annotated using HaploReg v4.1. Five sets of functional annotations were applied to determine the depression risk genes. The STRING database was used to expand the target genes and identify drug candidates from the DrugBank database. We validated the findings using the ClinicalTrial.gov and PubMed databases. Seven genes were observed to be strongly associated with depression (functional annotation score = 4). Interestingly, IL6R was auspicious as a target gene according to the validation outcome. We identified 20 drugs that were undergoing preclinical studies or clinical trials for depression. In addition, we identified sarilumab and satralizumab as drugs that exhibit strong potential for use in the treatment of depression. Our findings indicate that a genomic-analysis-based approach can facilitate the discovery of drugs that can be repurposed for treating depression.

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Functions of the Signal Transducer and Activator of Transcription 6 in a Behavioral Animal Model of Depression

Cited by 2 publications

References 15 publications

Brain region-dependent gene networks associated with selective breeding for increased voluntary wheel-running behavior

Brain region-dependent gene networks associated with selective breeding for increased voluntary wheel-running behavior

Genomic-Analysis-Oriented Drug Repurposing in the Search for Novel Antidepressants

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